Abstract

Background

There are striking similarities between the innate immune systems of invertebrates
and vertebrates. Caenorhabditis elegans is increasingly used as a model for the study of innate immunity. Evidence is accumulating
that C. elegans mounts distinct responses to different pathogens, but the true extent of this specificity
is unclear. Here, we employ direct comparative genomic analyses to explore the nature
of the host immune response.

Results

Using whole-genome microarrays representing 20,334 genes, we analyzed the transcriptional
response of C. elegans to four bacterial pathogens. Different bacteria provoke pathogen-specific signatures
within the host, involving differential regulation of 3.5-5% of all genes. These include
genes that encode potential pathogen-recognition and antimicrobial proteins. Additionally,
variance analysis revealed a robust signature shared by the pathogens, involving 22
genes associated with proteolysis, cell death and stress responses. The expression
of these genes, including those that mediate necrosis, is similarly altered following
infection with three bacterial pathogens. We show that necrosis aggravates pathogenesis
and accelerates the death of the host.

Conclusion

Our results suggest that in C. elegans, different infections trigger both specific responses and responses shared by several
pathogens, involving immune defense genes. The response shared by pathogens involves
necrotic cell death, which has been associated with infection in humans. Our results
are the first indication that necrosis is important for disease susceptibility in
C. elegans. This opens the way for detailed study of the means by which certain bacteria exploit
conserved elements of host cell-death machinery to increase their effective virulence.